Dickinson, M;
Kliszczak, AE;
Giannoulatou, E;
Peppa, D;
Pellegrino, P;
Williams, I;
Drakesmith, H;
(2020)
Dynamics of Transforming Growth Factor (TGF)-beta Superfamily Cytokine Induction During HIV-1 Infection Are Distinct From Other Innate Cytokines.
Frontiers in Immunology
, 11
, Article 596841. 10.3389/fimmu.2020.596841.
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Abstract
Human immunodeficiency virus type 1 (HIV-1) infection triggers rapid induction of multiple innate cytokines including type I interferons, which play important roles in viral control and disease pathogenesis. The transforming growth factor (TGF)-β superfamily is a pleiotropic innate cytokine family, some members of which (activins and bone morphogenetic proteins (BMPs)) were recently demonstrated to exert antiviral activity against Zika and hepatitis B and C viruses but are poorly studied in HIV-1 infection. Here, we show that TGF-β1 is systemically induced with very rapid kinetics (as early as 1–4 days after viremic spread begins) in acute HIV-1 infection, likely due to release from platelets, and remains upregulated throughout infection. Contrastingly, no substantial systemic upregulation of activins A and B or BMP-2 was observed during acute infection, although plasma activin levels trended to be elevated during chronic infection. HIV-1 triggered production of type I interferons but not TGF-β superfamily cytokines from plasmacytoid dendritic cells (DCs) in vitro, putatively explaining their differing in vivo induction; whilst lipopolysaccharide (but not HIV-1) elicited activin A production from myeloid DCs. These findings underscore the need for better definition of the protective and pathogenic capacity of TGF-β superfamily cytokines, to enable appropriate modulation for therapeutic purposes.
Type: | Article |
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Title: | Dynamics of Transforming Growth Factor (TGF)-beta Superfamily Cytokine Induction During HIV-1 Infection Are Distinct From Other Innate Cytokines |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.3389/fimmu.2020.596841 |
Publisher version: | https://doi.org/10.3389/fimmu.2020.596841 |
Language: | English |
Additional information: | © 2020 Dickinson, Kliszczak, Giannoulatou, Peppa, Pellegrino, Williams, Drakesmith and Borrow. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/). |
Keywords: | HIV, TGF-beta, activin, interferon, cytokine, dendritic cell, innate response, bone morphogenetic protein |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health > Infection and Population Health |
URI: | https://discovery.ucl.ac.uk/id/eprint/10131133 |
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